Investigating the molecular conformations of monoclonal antibodies (mAbs) adsorbed at the solid/liquid interface is crucial for understanding mAb solution stability and advancing the development of mAb-based biosensors. This study examines the pH-dependent conformational plasticity of a human IgG1k mAb, COE-3, at the SiO2/water interface under varying pH conditions (pH 5.5 and 9). By integrating neutron reflectivity (NR) and molecular dynamics (MD) simulations, we reveal that the mAb irreversibly deposits onto the interface at pH 5.5, with surface density saturation reached at 20 ppm bulk concentration. At pH 5.5, the adsorbed mAb adopts a stable “flat-on” orientation, while at pH 9, it assumes a more flexible conformation and a “tilted” orientation. This pH-dependent orientation shift is reversible and influenced by the distinct surface charge properties of the Fab and Fc fragments, with the Fc fragment more prone to desorption at higher pH. The root-mean-square deviation (RMSD) analysis further shows that COE-3 maintains structural stability upon adsorption across both pH levels, showing minimal unfolding or denaturation. These findings highlight how pH-dependent electrostatic interactions between mAb fragments and the SiO2 interface drive conformational adjustments in the intact mAb, offering insights into adsorption-induced aggregation and suggesting pH modulation as a mechanism for controlling biosensor efficiency.